A study published in The BMJ today suggests a link between newer contraceptive pills and higher risk of serious blood clots. The finding is not new, but it may be cause for a different kind of concern.

During their fertile years, between three and five women of every 10,000 who are not pregnant and not taking the pill are likely to develop blood clots every year. The research published today found older contraceptive pills double this “background” risk of blood clots, and the newer pills have roughly doubled the risk again.

Several studies published over the past 20 years show very similar findings. What this research brings to the table are larger numbers of women and more careful attention to factors in their medical history that could potentially skew the results.

It’s likely the media will pounce on this story; there will be testimonies from women who have experienced blood clots while taking the pill and a plethora of personal injury lawyers spruiking their business. Women across the world will be scared into stopping their contraception until it all blows over. I know this because I’ve seen it before, and I think that’s what we should be concerned about.

Back and forth

We’ve known the pill increases a woman’s risk of blood clots and stroke since it was first marketed. By the 1990s, concern had been tempered by the fact that this risk was greatly reduced by pills containing only a quarter of the oestrogen compared to the 1960s. The development of several newer progestogens in the 1980s had also increased the range of pills available, making it more likely that most women could find a combination that suited them.

But then, in 1995, three studies published in The Lancet suggested pills containing these newer progestogens posed twice the risk of blood clots as the older ones, just as the study published today does. Frenzied media coverage of the finding led many women to simply discontinue their contraception.

As a result, 1995-96 saw a 9% increase in abortion rates in Britain as well as a 25% increase in births. And both pregnancy and birth hold significantly higher risks of blood clots than any contraceptive pill, with rates at least ten times higher.

Within a few years, the controversy settled down somewhat when a number of epidemiologists pointed out that doubling an extremely small risk has no significant public health impact. But then, between 2007 and 2014, it all started again when a number of studies reached conflicting conclusions about whether there were any real differences in clotting rates between various pills.

Two very large studies that kept track of women from the time they started various pills showed no difference in blood-clotting risk between any of the pills the women were taking. But research like this is extremely expensive and only within the funding reach of either governments or pharmaceutical companies. In this case, it was the latter. Despite the fact that both studies were independently monitored, they were attacked as having commercial bias.

Four out of six of the remaining studies, which used various databases to look back from a blood clot diagnosis and capture the kind of pill the woman was taking, suggested the newer pills doubled risk. But the inevitable lack of “real-time” information in this kind of research also leaves it open to many potential biases.

The just-published BMJ study provides further evidence for research showing increased risk, and its publication will no doubt re-ignite the debate about the safety of newer contraceptive pills. It’s clearly time for an appraisal of the actual risks involved.

Being cautious

Even if we were to adopt the worst-case scenario from all the studies published to date, being on one of the older versions of the contraceptive pill increases the risk of blood clot from three and five per 10,000 women each year to somewhere between five and eight. Taking one of the newer ones raises it to between nine and 14.

So although a doubling of clotting risk sounds alarming, it actually translates to an additional four to six cases per 10,000 users of the newer pills a year.

It’s also important to recognise that only one in 100 women who have a blood clot will die from it. That risk of death could be cancelled out statistically by driving for two fewer hours each year. Put another way, the risk of a woman dying from a road accident is approximately 25 times that of death from a pill-related clot.

This is not to say we should be blasé about the risks posed by the contraceptive pill. It is above all a medication, which means some of its benefits may be compromised by – potentially serious – side effects. Every woman considering using the contraceptive pill should discuss the risks it poses to her health as well as available alternatives with her prescribing doctor.

This study adds to what is known about blood clot risk on various oral contraceptive pills, but it doesn’t claim to provide the definitive answer. I hope that, as we again debate the risks posed by the pill, we don’t lose sight of the fact that, for most women, the benefits of combined contraceptives far outweigh risks.

Terri Foran is Lecturer in the School of Women’s and Children’s Health at UNSW Australia.

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There’s been a lot of attention in the media about the number of children taking antipsychotic and other psychiatric medications. The assumption behind most of these stories is that these drugs are being overprescribed, and given to children with minor behavioral issues. A recent story in a European newspaper about the increased use of ADHD medications, for example, was headlined “Zombie Generation.” Yet the reality is there’s very little data to tell us the degree to which these medications are being used appropriately or not.

Antipsychotic medications, such as Risperdal, Seroquel and Abilify, were developed to treat adults with major mental illnesses including schizophrenia and bipolar disorder. But in recent years, their use has extended to treat conditions such as autism and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents.

How these medications work remains somewhat of a mystery, although we know they affect multiple brain neurotransmitters such as dopamine and serotonin.

Because these medications’ side effects include an increased risk for conditions such as obesity, diabetes and movement disorders, they’re subject to extra scrutiny to make sure that the right medications are being prescribed to the right patients at the right time.

For instance, the American Academy of Child and Adolescent Psychiatry has a list of 19 “best practice” recommendations. These include using just one medication at a time, avoiding the medications in very young children, monitoring for side effects, and trying other treatments first for things like ADHD and aggressive behavior.

Are doctors following prescribing guidelines?

With the rise in antipsychotic medication prescriptions, we wanted to know how well doctors were following these recommendations.

As a member of the Vermont Psychiatric Medications for Children and Adolescents Trend Monitoring workgroup, we were tasked with offering recommendations to our state legislature and other government agencies about psychiatric medication use in youth. We knew antipsychotic prescribing rates in Vermont had been somewhat high, but had dropped in recent years relative to other states. Without digging deeper, we couldn’t actually tell what this trend meant.

To learn more about why and when these medications are prescribed, we sent a survey to every provider who had prescribed an antipsychotic medication to a child covered by Medicaid in Vermont. We focused on Medicaid because we did not have access to commercial insurance databases.

Our survey was required in order for the prescription to be refilled, which meant our return rate (80%) was much higher that it would have been for a truly voluntary survey.

Clinicians aren’t always following guidelines

To our knowledge the study, which was recently published in Pediatrics, is the first one to compare antispychotic prescribing patterns to best practice guidelines.

We found evidence that these medications aren’t being doled out to treat minor behavioral problems, which is reassuring. But we also found places where doctors weren’t following best practice guidelines.

Perhaps the biggest finding was that an antipsychotic prescription followed best practice guidelines only about half the time. We also found that these medications were prescribed for an FDA-approved use only a quarter of the time.

By itself, this is bad news and means that there needs to be a greater effort to make sure these medications are being prescribed appropriately. Increasing access to child therapists who do evidence-based psychotherapy could help. So would making it easier for medical records to follow patients, particularly for kids in foster care who often move from place to place.

It turns out that most providers who prescribe antipsychotic medications are not psychiatrists. About half are primary care clinicians such as pediatricians or family physicians. And 42% of the time the doctor who is responsible for maintaining the antipsychotic medication isn’t the one who originally prescribed it. This can be a problem because a doctor may be less comfortable stopping a medication that someone else started. He or she also may not know the whole story behind why the child was prescribed the medication in the first place.

The most common reason by far that prescriptions failed to meet best practice standards was because the patient was not getting the recommended lab work – for instance, monitoring blood glucose to check for early diabetes. This is a problem, but there are other ways to monitor for potential side effects of these medications. And new electronic medical records may make it easier to remind doctors when these kinds of tests should be ordered.

Using antipsychotic drugs to treat bad behavior isn’t the norm

While some of the study’s results are discouraging, there is also good news. For example, using antipsychotic medications for relatively minor behavior problems – like temper tantrums in young kids – was relatively uncommon.

Further, over 90% of the time antipsychotic medications were being used only when other types of interventions, including different medications or psychotherapy, had failed. However, in many cases the type of psychotherapy tried first was not of a type that’s been shown to be most effective in treating the child’s particular problem.

And in cases when the patient was diagnosed with a condition that antipsychotic medications are not officially approved to treat, such as physical aggression, the behavior targeted was often something with scientific evidence to support using antipsychotic medication.

In our view, these medications do indeed have a place in treatment. But too many are getting to that place too quickly and without the appropriate level of monitoring. Our hope is that Vermont and other states will keep studying this issue and support doctors, patients and families to ensure that these medications are being used appropriately and safely.

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This year marks the 50th anniversary of cisplatin’s accidental discovery as an anti-cancer drug. Despite its horrible side effects, and the ability of cancers to become resistant to it, the drug remains as relevant now as it was when it first reached the market.

And the good news is that the drug can, and is, being made better. New formulations are being designed to make it more effective and less toxic.

The history of cisplatin

The history of cisplatin starts not in 1965, but in 1844, when it was first created by Italian chemist Michele Peyrone. For a long time it was known as Peyrone’s chloride. But the really important event was its accidental discovery as a cancer treatment by Barnett Rosenberg, a biophysical chemist.

At the time, Rosenberg was trying to study the effect electric fields had on bacterial growth. During his experiments, he found bacteria grew 300 times their normal size, a very unusual result, when he used platinum electrodes to generate the electric fields. It took a while to figure out what was going on, but in the end he discovered the platinum electrodes were corroding in the test solution, producing cisplatin.

Rosenberg published his remarkable findings in the journal Nature and followed this up three years later with another paper showing cisplatin could cure tumours in mice.

Cisplatin has been used as a treatment for cancer since its approval by the US Food and Drug Administration in 1978. And while five other platinum drugs based on the structure of cisplatin have been developed since, it has never been replaced.

Platinum drugs are now used in 40% of all chemotherapy treatments. This has completely changed how some cancers are treated. For instance, before cisplatin’s discovery the cure rate of testicular cancer was just 10%, but when combined with early detection the cure rate is now approaching 100%.

The good and the bad

Cisplatin has to be given as an intravenous injection because it’s not effective when delivered orally. Once in the veins, it moves from the blood stream into cancer cells where it bonds with water to form a more reactive form of the drug.

In this form, the drug can stop DNA from replicating and from acting as a blueprint for making proteins. This causes cancer cells to recognise something is wrong and initiate a type of cell suicide called apoptosis.

But cisplatin is not without its problems. Its suite of horrible side effects includes severe nausea and vomiting. These two side effects are, in fact, so bad that the drug’s development was almost stopped when it was first tested on people. It was only the invention of effective anti-nausea drugs that led to cisplatin’s approval by drug authorities.

Cisplatin also makes patients anaemic and susceptible to infections. It destroys their kidneys too, although giving the patient lots of water before and after treatment has been found to be effective in reducing this.

Worse still, because these side effects are so severe, they limit the dose of the drug that can be given to patients. Many cancers end up getting treated with less than optimal doses as a result, which leads to tumours rapidly developing resistance to further treatment. This is a particular problem in the treatment of ovarian cancer because it develops resistance faster than other types of cancer.

The future of cisplatin

But there’s good news on this front. Over the last two decades, many researchers, including my research team, have been developing new formulations of cisplatin in an effort to reduce its side effects. The best way to do this is through the use of nanoparticles to better target cisplatin to cancer cells. Better targeting cancer drugs is important so they don’t attack non-cancerous tissue.

One such nanoparticle formulation being commercially developed is Lipoplatin. This formulation encloses cisplatin in a shell called a liposome, which is similar in structure to the walls of human cells. As a result, it floats in the bloodstream for longer and gets trapped selectively in tumours but not normal tissue.

And it doesn’t stop there. Novel nanoparticle formulations of cisplatin using exotic materials are also being developed, although these are much further away from being ready for human testing. To date, cisplatin has been attached to carbon nanotubes, gold nanoparticles and even spaghetti ball-like polymers called dendrimers.

My team has also attached cisplatin to the outside of nanoparticles made of rust. Because rust contains iron, we could control the movement of the nanoparticles with magnets, ensuring the drug only goes to the sites in the body where it’s needed.

This drug has revolutionised the treatment of many types of cancer, especially testicular, and remains as critically important now as when it was first discovered. So happy 50th anniversary to cisplatin and good luck to all those working to make it better.

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